Analysis of gut microbiota changes in APAP induced liver injury in mice based on 16S rDNA sequencing technology
Objective To analyze the changes of gut microbiota during drug-induced liver injury(DILI)in mice induced by acetaminophen(APAP)using 16S rDNA sequencing technology,and to explore the possible mechanism of DILI in mice.Method 20 male C57BL/6N mice were randomly divided into control group and APAP group.The APAP group was ig with APAP(600 mg·kg-1)to bulid the DILI mouse model,while the control group was ig with an equal amount of 0.5％carboxymethyl cellulose sodium(CMC-Na)solution.After 14 consecutive days,the contents or activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipopolysaccharide(LPS),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum were determined under anesthesia.HE staining to observe the pathological changes of the liver and intestines.16S rDNA sequencing to analyze the composition and structure of fecal gut microbiota.Results Compared with the control group,the contents or activities of ALT,AST,LPS,TNF-α and IL-6 in serum of APAP group were significantly increased(P＜0.01),a large number of eosinophilic changes and obvious inflammatory infiltration cell were observed in liver cells.Glands in the ileum and colon mucosa were shrunk.The structure of intestinal microbiota was disordered,the relative abundance of Proteobacteria,Actinobacteria,and Acinetobacter were significantly increased(P＜0.01),the relative abundance of Verrucomicrobia,Akkermansia and Shannon index were decreased significantly(P＜0.01,0.05).Conclusion The structure and composition of intestinal microbiota in mice with DILI induced by APAP have undergone changes.APAP may increase intestinal permeability and lead to endotoxin leakage by disrupting intestinal microbiota homeostasis and intestinal barrier,exacerbating DILI.
NETL
NSTL
万方数据
维普
